The major aim is to determine the mechanisms of the biosynthesis and interconversion of purine nucleotides and their derivatives in microorganisms. Auxotropic mutants are used to unravel the essential steps, to obtain genetic modification of the reactions, and to determine the interplay of purine biosynthesis and interconversions with other essential metabolites. Genetic control of the expression of the enzymes is studied by identifying multigenic units of functional control and determining the regulatory elements which control the expression of the genes. Particular attention will be placed on the metabolic mechanisms which regulate these processes, the genetic devices which alter them, and mutational events which impair or modify their regulation. Molecular cloning techniques will be used to facilitate determination of genetic organization and identification of regulatory regions. The special reactions under consideration include, 1) the multi-enzyme system involved in the formation of the first biosynthetic intermediate, phosphoribosylamine, 2) the inosinate cyclohydrolasetransformylase complex, 3) phosphoribosyl-aminoimidazole carboxylase, 4) guanosine monophosphate reductase, 5) purine phosphoribosyltransferases, and 6) other salvage and interconversion enzymes such as purine nucleotide phosphorylase and kinases.